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One hundred and sixteen patients with locally advanced or metastatic breast cancer were randomized to receive CMF (cyclophosphamide 600 mg m(-2) day 1 and 8 i.v., 5-fluorouracil 600 mg m(-2) day 1 and 8 i.v., methotrexate 40 mg m(-2) day 1 and 8 i.v., monthly for 6 cycles) or MM (methotrexate 30 mg m(-2), mitoxantrone 6.5 mg m(-2), both i.v. day 1 3-weekly for 8 cycles) as first line treatment with chemotherapy. Objective responses occurred in 17 patients out of 58 (29%) who received CMF and nine out of 58 (15%) who received MM; 95% confidence interval for difference in response rates (-1%-29%), P = 0.07. No statistically significant differences were seen in overall survival or time to progression between the two regimes although a tendency towards a shorter progression time on the MM regime must be acknowledged. There was, however, significantly reduced haematological toxicity (P < 0.001) and alopecia (P < 0.001) and fewer dose reductions and delays in patients randomized to MM. No statistically significant differences were seen between the two regimes in terms of quality of life (QOL). However, some association between QOL and toxicity was apparent overall with pooled QOL estimates tending to indicate a worsening in psychological state with increasing maximum toxicity over treatment. Despite the fact that results surrounding response rates and time to progression did not reach statistical significance, their possible compatibility with an improved outcome on CMF treatment must be borne in mind. However, MM is a well-tolerated regimen with fewer side-effects than CMF, which with careful patient management and follow-up, therefore, may merit consideration as a first-line treatment to palliate patients with metastatic breast cancer who are infirm or elderly. [ABSTRACT FROM AUTHOR]

One hundred and sixty-four patients with Graves' disease were treated with low-dose radioiodine (2 mCi), with a mean follow up of 41/2 years. At this time 74 (45%) were euthyroid having had a single dose, with a total of 131 (80%) being controlled with one or more doses. Three (2%) were still toxic but their mean follow up was only 3 years. Thirty (18%) were rendered hypothyroid, two-thirds of these after a single dose of 2 mCi 131I. The one-year incidence of hypothyroidism was 6%, with an incidence at 6 years of 20%. Previous surgery, medical treatment and thyroid antibody status appeared to have no influence on the outcome. [ABSTRACT FROM AUTHOR]

Abstract: Rectal squamous cell carcinoma is a rare tumour accounting for only 0.25% of all rectal carcinomas, yet it carries a significant mortality and morbidity. Radical surgery has been advocated as the primary treatment modality with or without adjunctive therapies despite the proven benefits of primary chemoradiotherapy for squamous cell carcinoma (SCC) of the anus. This report describes 7 cases of rectal squamous cell carcinoma from a single institution over a four-year period, treated with primary chemoradiotherapy. All patients demonstrated significant tumour regression, and surgery to the primary tumour was avoided in all but one of these cases. Primary chemoradiotherapy can achieve excellent local control for rectal squamous cell carcinoma with surgery employed only for unresponsive or recurrent tumours. [Copyright &y& Elsevier]

Background: Brain metastases are common in human epidermal growth factor receptor (Her)-2-positive breast cancer. Drug access to brain metastases and normal brain is key to management of cranial disease. In this study, positron emission tomography (PET) scanning after administration of radiolabelled lapatinib was used to obtain direct evidence of cranial drug access., Methods: Patients with Her-2+ metastatic breast cancer either with at least one 1-cm diameter brain metastasis or without brain metastases underwent dynamic carbon-11 radiolabelled lapatinib ([(11)C]lapatinib)-PET. Less than 20 μg of [(11)C]lapatinib was administered before and after 8 days of oral lapatinib (1,500 mg once daily). Radial arterial blood sampling was performed throughout the 90-min scan. The contribution of blood volume activity to the tissue signal was excluded to calculate lapatinib uptake in normal brain and metastases. Partitioning of radioactivity between plasma and tissue (V T) was calculated and the tissue concentration of lapatinib derived. Plasma lapatinib levels were measured and adverse events noted., Results: Six patients (three with brain metastases) were recruited. About 80% plasma radioactivity corresponded to intact [(11)C]lapatinib after 60 min. PET signal in the brain corresponded to circulating radioactivity levels, with no [(11)C]lapatinib uptake observed in normal brain tissue. In contrast, radioactivity uptake in cranial metastases was significantly higher (p = 0.002) than that could be accounted by circulating radioactivity levels, consistent with [(11)C]lapatinib uptake in brain metastases. There was no difference in lapatinib uptake between the baseline and day 8 scans, suggesting no effect of increased drug access by inhibition of the drug efflux proteins by therapeutic doses of lapatinib., Conclusions: Increased lapatinib uptake was observed in brain metastases but not in normal brain., Trial Registration: ClinicalTrials.gov: NCT01290354.

Background: Advanced colorectal cancer is treated with a combination of cytotoxic drugs and targeted treatments. However, how best to minimise the time spent taking cytotoxic drugs and whether molecular selection can refine this further is unknown. The primary aim of this study was to establish how cetuximab might be safely and effectively added to intermittent chemotherapy., Methods: COIN-B was an open-label, multicentre, randomised, exploratory phase 2 trial done at 30 hospitals in the UK and one in Cyprus. We enrolled patients with advanced colorectal cancer who had received no previous chemotherapy for metastases. Randomisation was done centrally (by telephone) by the Medical Research Council Clinical Trials Unit using minimisation with a random element. Treatment allocation was not masked. Patients were assigned (1:1) to intermittent chemotherapy plus intermittent cetuximab or to intermittent chemotherapy plus continuous cetuximab. Chemotherapy was FOLFOX (folinic acid and oxaliplatin followed by bolus and infused fluorouracil). Patients in both groups received FOLFOX and weekly cetuximab for 12 weeks, then either had a planned interruption (those taking intermittent cetuximab) or planned maintenance by continuing on weekly cetuximab (continuous cetuximab). On RECIST progression, FOLFOX plus cetuximab or FOLFOX was recommenced for 12 weeks followed by further interruption or maintenance cetuximab, respectively. The primary outcome was failure-free survival at 10 months. The primary analysis population consisted of patients who completed 12 weeks of treatment without progression, death, or leaving the trial. We tested BRAF and NRAS status retrospectively. The trial was registered, ISRCTN38375681., Findings: We registered 401 patients, 226 of whom were enrolled. Results for 169 with KRAS wild-type are reported here, 78 (46%) assigned to intermittent cetuximab and 91 (54%) to continuous cetuximab. 64 patients assigned to intermittent cetuximab and 66 of those assigned to continuous cetuximab were included in the primary analysis. 10-month failure-free survival was 50% (lower bound of 95% CI 39) in the intermittent group versus 52% (lower bound of 95% CI 41) in the continuous group; median failure-free survival was 12.2 months (95% CI 8.8-15.6) and 14.3 months (10.7-20.4), respectively. The most common grade 3-4 adverse events were skin rash (21 [27%] of 77 patients vs 20 [22%] of 92 patients), neutropenia (22 [29%] vs 30 [33%]), diarrhoea (14 [18%] vs 23 [25%]), and lethargy (20 [26%] vs 19 [21%])., Interpretation: Cetuximab was safely incorporated in two first-line intermittent chemotherapy strategies. Maintenance of biological monotherapy, with less cytotoxic chemotherapy within the first 6 months, in molecularly selected patients is promising and should be validated in phase 3 trials., (Copyright © 2014 Wasan et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.)

Background: Data on the natural course of patients with breast cancer and schizophrenia are limited. Although there have been studies in assessing the incidence of breast cancer in the setting of schizophrenia, there is very little information concerning the clinical profile of these women., Methods: We analyzed the data from our electronic notes system by searching for the terms 'schizophrenia' or 'schizophrenic' and 'breast cancer' or 'tumour' between 1993 and 2009. Information was collected on demographics, clinico-pathologic disease variables, treatment including anti-emetic use, chemotherapy delivery and outcomes., Results: From 90,676 patients screened, we identified 37 individuals who had breast cancer and a pre-existing underlying diagnosis of schizophrenia. Of these, 30 (81%) presented with early breast cancer and 7 (19%) presented with metastatic disease. Node positivity was observed in 14 individuals (38%). The average interval between diagnosis of schizophrenia and breast cancer was more than 20 years in the majority of the patients. Treatment outcomes, trial involvement, compliance and ability to provide informed consent were similar to our previously published cohort data., Conclusions: Schizophrenia does not affect treatment delivery or outcomes in women with breast cancer. The presence of schizophrenia should not be a limiting factor for entry into clinical trials. Breast cancer patients with this illness should be offered standard treatment without discrimination, including entry into clinical trials., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Purpose: Novel radiotracers could potentially allow the identification of clinically aggressive tumor phenotypes. As choline metabolism increases during malignant transformation and progression of human mammary epithelial cells, we examined the ability of [(11)C]choline (CHO) positron emission tomography imaging to detect clinically aggressive phenotype in patients with estrogen receptor (ER)-positive breast cancer in vivo., Experimental Design: CHO positron emission tomography was done in 32 individuals with primary or metastatic ER-positive breast cancer. Semiquantitative (standardized uptake value) and fully quantitative (net irreversible transfer rate constant of CHO, Ki) estimates of CHO uptake in the tumors were calculated and compared with tumor grade, size, involved nodes, and also ER, progesterone receptor, Ki-67, and human epidermal growth factor receptor-2 scores., Results: Breast tumors were well visualized in 30 of 32 patients with good tumor background ratios. A wide range of uptake values were observed in primary and metastatic tumors. CHO uptake variables correlated well with tumor grade. For most imaging variables, a poor association was found with tumor size, ER, progesterone receptor, human epidermal growth factor receptor-2, Ki-67, and nodal status., Conclusions: CHO showed good uptake in most breast cancers and merits further investigation as a breast cancer imaging agent.

The objective of this study was to evaluate the clinical response of locally advanced breast cancer (LABC) to neoadjuvant (NA) chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and to study the role of docetaxel in patients who fail to respond to first-line chemotherapy. Patients were enrolled who had primary tumours without distant metastasis that were too extensive for conservative surgery. All underwent NA chemotherapy for breast cancer and thereafter surgery and/or radical radiotherapy. NA chemotherapy with FEC was administered to 88 patients between February 1998 and June 2005. A median of 6 cycles of FEC (range 1-8) was given, followed in 21 cases by a median of 4 cycles (range 2-6) of docetaxel. Where clinically established, with FEC the clinical complete response (cCR) was 22/81 (27%), clinical partial response (cPR) 41/81 (51%), clinical stable disease (cSD) 18/81 (22%). In patients where the response to FEC was regarded as insufficient, docetaxel was given. Response rates were cCR 3/21 (14%); cPR 10/21 (48%), cSD 8/21 (38%). There were 11 cases of pathological complete response (pCR), 9 in the FEC-only group and 2 in the docetaxel group. Following chemotherapy 49 (56%) patients underwent mastectomy, 32 (36%) breast conserving surgery and 5 (6%) radical radiotherapy, giving a breast conservation rate of 42%. Two patients died before receiving surgery or radical radiotherapy. The results show that neoadjuvant FEC is a reasonable NA therapy in breast cancer and that docetaxel is effective in FEC refractory cases. Only 8 of 81 (10%) assessable patients did not respond to any chemotherapy, giving an overall clinical response rate of 90%, which is comparable to studies in which taxanes were given irrespective of response to preceding therapy with antracycline including regimes.

The risk of carcinogenesis from radiation exposure is well known. It has been questioned for some time therefore, whether it is wise to treat benign disease with radiotherapy. We report a case of a patient who developed bilateral breast carcinomas almost 30 years after treatment of chest wall keloids with radiotherapy. There are only anecdotal reports in the literature of malignancies following treatment of keloids with radiotherapy. We review these reports and discuss the safety of this approach to the management of keloid scars.

Cases of myelodysplastic syndrome occurring after multi-drug chemotherapy are rare; they are more often associated with the use of alkylating agents. We report the case history of a patient with myelodyspasia occurring after neoadjuvant methotrexate, mitoxantrone and mitomycin C (triple M) chemotherapy with subsequent radiotherapy for locally advanced breast cancer. Cytogenetic analysis of a bone marrow biopsy confirmed the typical chromosomal abnormalities associated with therapy related myelodysplasia. Few treatments for this disorder have been found to be of value. The aetiology, incidence and management options are briefly discussed.

It is unusual to obtain responses after two different sequential regimens in patients with metastatic breast cancer. In this retrospective analysis, data were examined on 22 patients who had already received two or three different regimens for metastatic breast cancer before being treated with 100 mg/m2 docetaxel (or 75 mg/m2 if clinically warranted). 13 patients received three or more courses and 21 patients were assessable for response. 5 of 21 assessable patients (24%) responded for 3-11 months and a further 6 (29%) stabilised. Toxicity (WHO grade 3 and/or 4), principally neutropenia, stomatitis and fluid retention, occurred in 10 patients. We conclude that docetaxel is an active agent in heavily pretreated patients with metastatic breast cancer, but care should be taken to minimise side-effects in this group of patients.

The activity of paclitaxel has been extensively investigated in previously treated patients with metastatic breast carcinoma. We evaluated the activity of paclitaxel as primary medical therapy in patients with stage III and IV breast carcinoma, 6 female patients were recruited with no previous history of surgery, radiotherapy or chemotherapy. Paclitaxel was administered as a 3-h infusion at a dose of 225 mg/m2 repeated every 3 weeks weekly to a maximum of 10 cycles. 2 patients achieved a complete response, one of whom had a normal trucut biopsy of the affected breast 6 months after discontinuation of chemotherapy and radiotherapy and a normal mammogram at 17 months. 3 patients achieved a partial response and one stabilised. The patients received between four and ten cycles of chemotherapy. Paclitaxel at this dose was associated with toxicity including alopecia, stomatitis, nausea and diarrhoea. Moderately severe neutropenia occurred in 4 patients, 2 requiring antibiotics but was of short duration and did not necessitate a dose reduction for subsequent courses. Paclitaxel has shown activity as primary medical therapy in patients with inoperable breast carcinoma at presentation at this dosage and schedule. One patient achieved a complete response and avoided surgery altogether and all 6 patients had their primary tumour downgraded. It may be indicated as a single agent in this context or in combination with other drugs with proven activity in breast carcinoma.

Interstitial photodynamic therapy has a number of potential advantages over superficial treatment. We have treated 50 subcutaneous and cutaneous tumours interstitially, in nine patients. An additional 22 tumours in the same patients, were treated by superficial PDT. Patients received 1.5-2.0 mg kg-1 of polyhaematoporphyrin and 72 h later underwent treatment using a copper vapour dye laser producing red light at 630 nm. All interstitial treatments were delivered using cylindrical diffusing fibres and a wide range of light doses (5-1500 J cm-3). The complete response rate for all tumours treated interstitially was 52%, rising to 81% in those patients who received 2.0 mg kg-1 PHP and light doses in excess of 500 J cm-3. The overall incidence of skin necrosis was 32% and was 79% in those treated with light doses of greater than 500 J cm-3. The incidence of skin necrosis with interstitial PDT is lower than that seen with superficial photodynamic therapy but higher volumetric light doses are required to produce tumour complete responses. All treatments were well tolerated and volumes of tumour up to 60 cm3 were successfully treated. The penetration depth of 630 nm light in human breast cancer tissue was determined as 4 mm. Little true tumour tissue selectivity was detected by analysis of porphyrin levels in biopsy material.

Non-Hodgkin's lymphomas are an increasing problem in the AIDS population. They are generally aggressive, high-grade lymphomas and more commonly present at extranodal sites, particularly the central nervous system. Although chemo- and radiosensitive, the duration of response is generally short lived. Spontaneous remission of non-Hodgkin's lymphomas has been reported in immunocompetent individuals, but has not been reported in HIV disease. We would like to report the first such case.

Biopsy specimens of the gastric antrum, duodenum, and rectum from three patients with secondary amyloidosis were examined by electron microscopy in an attempt to determine the ultrastructural distribution of amyloid filaments and to identify any secondary changes in the covering mucosal epithelial cells. The characteristic amyloid filaments were seen in the walls of submucosal arterioles and mucosal capillaries deposited within the basal lamina surrounding the endothelial cells. Filaments were also sometimes seen within the muscularis mucosa. the overlying gastric and rectal epithelial cells appeared normal, but numerous curved bacilli were seen in close contact with the microvilli of the surface epithelial gastric cells. Duodenal columnar absorptive cells were vacuolated and contained prominent lysosomes. These changes are probably degenerative and may explain, at least in part, the development of malabsorption in some patients with intestinal amyloidosis.

A case of angiosarcoma arising in an arm affected by chronic lymphoedema and treated initially by intraarterial cytotoxic perfusion chemotherapy and radiotherapy is described. The patient is still alive twenty years after presentation. This represents the longest reported survival for this condition.

One hundred and sixty-four patients with Graves' disease were treated with low-dose radioiodine (2 mCi), with a mean follow up of 4 1/2 years. At this time 74 (45%) were euthyroid having had a single dose, with a total of 131 (80%) being controlled with one or more doses. Three (2%) were still toxic but their mean follow up was only 3 years. Thirty (18%) were rendered hypothyroid, two-thirds of these after a single dose of 2 mCi 131I. The one-year incidence of hypothyroidism was 6%, with an incidence at 6 years of 20%. Previous surgery, medical treatment and thyroid antibody status appeared to have no influence on the outcome.